Microlicensing particles and applications

ABSTRACT

A microscopic lens, of size approximately 1 micron is used for its optical characteristics.

RELATED APPLICATIONS

This application claims the benefit of the U.S. Provisional ApplicationNo. 60/108,585, filed on Nov. 12, 1999.

GOVERNMENT CONTRACTS

The work described in this application was supported by Grant No.PHY97-22417 awarded by the National Science Foundation.

BACKGROUND

Spherical polymer microspheres can be mass produced with extraordinaryprecision and low cost. Many uses for these microspheres have beendeveloped that rely on the specific binding of a microsphere to atarget, and the labelling of the polymer microsphere with various dyesor magnetic material.

Spherical glass lenses greater than 1 mm in diameter are used forcoupling light into or out of fibers as well as for relaying imagesacross a short distance.

The present application describes new optical applications of sphericalpolymer microspheres less than 10 microns in diameter.

SUMMARY

The present application teaches a special microlensing particle andapplications of the particle. According to the present invention, alatex microsphere of diameter 0.3 μm-4 μm is obtained. Latexmicrospheres of this type are commercially available and have been usedin pregnancy tests and other applications that do not exploit theiroptical properties.

According to the present system, the latex microsphere is preferablyless than 10 μm in diameter, more preferably 1 to 2 μm in diameter. Thelatex microsphere is used in combination with an optical imagingelement.

Applications of the latex microsphere include a micro lensing rotationalprobe for use in detecting high frequency rotational motion, a scanningmicroscope, and a diode laser collimator device.

BRIEF DESCRIPTION OF THE DRAWINGS

These and other aspects will now be described in detail with respect tothe accompanying drawings, wherein:

FIG. 1 shows a diagram of the optical microsphere;

FIG. 2A shows optical ray tracing of dual microspheres;

FIG. 2B shows the microspheres arranged in an enhanced signal mode;

FIG. 3 shows a block diagram of the electronics used in the rotationdetector;

FIG. 4 shows an optical microscope formed with a microsphere lens;

FIG. 5 shows a laser with a microsphere lens;

FIG. 6 shows a fiber with a microsphere lens.

DETAILED DESCRIPTION

FIG. 1 shows the use of a miniature optical element, e.g., a spheroidelement, e.g. a microsphere, to change the characteristics of incominglight. The optical microsphere 100 is a latex sphere or spheroid body,which has at least one round cross section, and in which the diameter Dof the round cross section is between 0.8 and 2 μm. More generally, theLatex particles of this type are commercially available from Bangs, orInterfacial Dynamics Corporation, or other companies.

It was found by the present inventors that the latex sphere has acollimating effect on incoming light. Incoming light 110 is collimatedby the sphere into collimated light 120. The collimated light can beused for various purposes described herein.

A first embodiment is used to sense high frequency rotational motion. Anasymmetric fluorescent probe is formed of a microsphere pair 199 asshown in FIG. 2A. The probe includes a first latex microsphere 200 inoptical and physical contact with a second latex microsphere 210. Thefirst microsphere 200 is approximately 1.1 μm in diameter and forms alensing portion. The smaller microsphere 210, which can be between 0.5μm and 1 μm, is fluorescently-labeled. The larger microsphere 200 actsas a lens that enhances the collection efficiency of the optical system.

The two microspheres are connected together. Light is passed by theoptical combination of the two spheres. FIG. 2A shows optical raytracing of the two microspheres. The ray originally starts at an angle θrelative to the vertical 220. After passing through the lensingmicrosphere 200, the ray continues at an angle φ′−θ″. If the lens is inwater, the index of refraction of the water, n₁, is 1.3. The microsphere200 has an index of refraction, n₂, =1.59 (for polystyrene). Aphotodetector 225 monitors for the proper fluorescence from the markedsphere 210.

When the microsphere pair 199 is oriented relative to the photodetector225 as shown in FIG. 2A, light passes through the flourescently-markedmicrosphere 210 directly to the photodetector 225, and a relatively dimsignal of the marked sphere 210 is obtained.

FIG. 2B shows the microsphere pair oriented in alignment with theoptical collection axis 220. In this situation, the fluorescence fromthe marked microsphere, or objective 210 is enhanced by the lensingaction of the lens 200. The amount of collected light indicative of themarked lens is enhanced. This can be seen according to a geometricoptics argument.

The angles of ray tracing are outlined in FIG. 2A The exit angle φ′−θ″can be calculated as a function of the incident angle θ. The fluorescentmicrosphere 210 is approximated as a point particle located a distance δfrom the lensing microsphere. Using geometry, it can be seen thatφ′=π−(π2θ′+φ)=2θ−φ

Applying Snell's law at the top interface of the lensing microsphere:$\theta^{''} = {\sin^{- 1}\left( {\frac{n_{2}}{n_{1}}\sin\quad\theta^{\prime}} \right)}$where n₂ is the index of refraction of the lensing microsphere and n₁ isthe index of refraction of the surrounding medium (typically water).Applying Snell's law at the bottom interface gives$\theta^{\prime} = {\sin^{- 1}\left( {\frac{n_{2}}{n_{1}}{\sin\left( {\theta + \phi} \right)}} \right)}$

Then, direct substitution of equation (3) into equation (2), shows thatθ″=φ+θ

Using the law of sines, this can be rewritten as${\frac{\sin\left( {\pi - {{\theta--}\phi}} \right)}{r + \delta} = \frac{{\sin\quad\theta}\quad}{r}},$

and then explicitly find the angle φ as a function of${\phi\left( {r,\theta,\delta} \right)} = {{\sin^{- 1}\left( {\frac{r + \delta}{r}\sin\quad\theta} \right)} - {\theta.}}$

Finally, the exit angle φ′−θ″ can be written in terms of the originalangle θ, the radii of the two spheres, r, δ, and the indices ofrefraction, n₁ and n₂.${\phi^{\prime} - \theta^{\prime\prime\prime}} = {{2\quad{\sin^{- 1}\left( {\frac{n_{1}}{n_{2}}{\sin\left( {\theta + {\phi\left( {r,\theta,\delta} \right)}} \right)}} \right)}} - \theta - {2{{\phi\left( {r,\theta,\delta} \right)}.}}}$

For δ<<t, φ<<θ. The exit angle is then given by${\phi^{\prime} - \theta^{\prime\prime}} = {{2\quad{\sin^{- 1}\left( {\frac{n_{1}}{n_{2}}\sin\quad\theta} \right)}} - {\theta.}}$

Typical realizable values of n₁ and n₂ are for water, n₁=1.3 andpolystyrene, n₂=1.59. For small θ, the equation above reduces to$\left( {{2\frac{n_{1}}{n_{2}}} - 1} \right){\theta.}$This gives an exit angle of 0.64•θ for a ray entering at an angle θ.Since the exit angle is always less than the original angle, the lensingmicrosphere focuses rays from the fluorescent microspheres and enhancesthe optical signal.

The enhancement in the observed optical signal also depends on thenumerical aperture of the objective. The numerical aperture (NA) isdefined as NA=n sin θ₀, where θ₀ is the collection angle. For thepresent objective (20×, 0.4 NA) in air θ₀=23.6°. The equation shows thatthe focusing microsphere increases the angle of collection to 43.5°.This corresponds to an effective NA of 0.69. The epi-fluorescentintensity in proportional to NA⁴, so the intensity enhancement shouldrelate (0.69/0.4)⁴≈9 times.

FIG. 3 shows a block diagram of the electronics of the system. A lightsource 300 shines light along an optical axis 305. The microsphere pair199 is located along this optical axis 305. Light which shines throughthe microsphere pair impinges on a photodetector 310 which produces asignal 315 indicative of the amount of incoming light. This signal 315is coupled to a controller element 320 such as a processor. Theprocessor measures the signal amplitude of the flourescently-markedportion of the light. From this amplitude, the processor calculateseither an orientation angle of the pair 199, or more simply a signalindicative of the rate of change of that orientation angle.

The rate of change indicates the rate of rotation of the pair 199.

The above has described one embodiment of these miniature lenses, butother applications are also possible.

FIG. 4 shows the microlensing particle used in an optical scanningmicroscope. The microsphere lens 100 is held within optical tweezers 400over a surface 415 to be scanned. The lens is indexed by an indexer 410to scan the device across the surface 415. The surface can beilluminated by a lamp 420, causing light to reflect off the surface.Alternatively, the light from lamp 420 can cause fluorescence of thematerials on the surface 415.

The light reflected from the surface, shown as 425, produces an output430 which is collimated when the microsphere is directly above thesurface area being imaged.

The microlens enhances the numerical aperture of the objective 440 ofthe microscope 438. This enables the microscope to have a high numericalaperture combined with a long working distance. Such a microscope avoidsthe usual trade off between light collecting capability (numericalaperture) and working distance.

In one mode, the microlens 100 can actually be smaller than thewavelength of light that is used. This allows the microscope to resolveat a resolution that is higher than the diffraction limit of theradiation.

Another application of the microlens is shown in FIG. 5. Diode lasersare often small devices which produce a laser output over a very smallscale. The laser output is often Gaussian.

A diode laser relies on two mirrors shown as 500 and 502 to form alasing cavity 504. The present embodiment attaches microlens 506directly on the output mirror 508. This helps collimate the laser beam510. Moreover, since the laser itself is often on the order of size of10 μm, a microscopic lens can help collimate almost all of the outputlight from the laser while minimally adding to the size of the laser.

FIG. 6 shows an optical fiber 600 using light collimated by a lens, toconverge on the fiber end 605. In this embodiment, microsphere lens 100is coupled directly onto the end of the fiber, and centered on the endof the fiber. The microsphere increases the effective numerical apertureand hence improves the coupling efficiency of the light.

In the embodiments of FIGS. 5 and 6, the lens can be attached to thedesired surface, using a biochemical glue such as avidin or biotin, tohold the lens in place. Alternatively, the lens could be properlypositioned with optical tweezers, and melted or welded into place.

Other modifications are contemplated.

1-4. (canceled)
 5. A device as in claim 23, where said lensing elementis made of polystyrene latex.
 6. A device as in claim 23, where saidlensing element is made of glass.
 7. A device as in claim 23 furthercomprising multiple lens elements attached together. 8-22. (canceled)23. An optical device comprising: a spherical lensing element having adiameter of 10 μm or less, the spherical lensing element configured tocollimate incident light to generate a collimated light beam; and anoptical imaging element receiving the collimated light beam.
 24. Theoptical device of claim 23 wherein the incident light is emitted from asurface of an object that is to be imaged.
 25. The optical device ofclaim 24 wherein the lensing element is configured to receive theincident light generated by fluorescence of the object.
 26. The opticaldevice of claim 24 wherein the optical imaging element comprises aphotodetector.
 27. The optical device of claim 24 wherein the diameterof the optical imaging element is smaller than a wavelength of theincident light, thereby enabling a resolution greater than a diffractionlimit of the radiation.
 28. The optical device of claim 24 furthercomprising optical tweezers holding the lensing element over thesurface.
 29. The optical device of claim 23 wherein the lensing elementis configured to receive a laser beam emitted by a laser.
 30. Theoptical device of claim 29 wherein the lensing element is positioned onan output mirror of the laser.
 31. The optical device of claim 29wherein the laser is a diode laser emitting a laser beam having a widthof less than 10 μm, such that the entire width of the laser beam iscollimated by the lensing element.
 32. The optical device of claim 23end of an optical fiber.
 33. The optical device of claim 32 wherein thelensing element is positioned on the end of the optical fiber.
 34. Theoptical device of claim 32 wherein the lensing element is configured toimprove a coupling efficiency of the light.
 35. A method of focusinglight comprising collimating incident light with a spherical lensingelement having a diameter of 10 μm or less.
 36. The method of claim 35wherein the incident light is emitted from a surface of an object thatis to be imaged.
 37. The method of claim 36 wherein the incident lightis reflected from the surface.
 38. The method of claim 36 wherein theincident light is generated by fluorescence of the object.
 39. Themethod of claim 36 wherein the diameter of the optical imaging elementis smaller than a wavelength of the incident light, thereby enabling aresolution greater than a diffraction limit of the radiation.
 40. Themethod of claim 36 further comprising holding the lensing element overthe surface with optical tweezers.
 41. The method of claim 35 whereinthe incident light is a laser beam.
 42. The method of claim 41 furthercomprising positioning the lensing element on an output mirror of alaser generating the laser beam.
 43. The method of claim 41 wherein thelaser beam is emitted from a laser diode and has a width of less than 10μm, such that an entire width of the laser beam is collimated by thelensing element.
 44. The method of claim 35 further comprisingpositioning the lensing element on an end of an optical fiber such thata coupling efficiency of the incident light is achieved.